It has been proposed that activation of Toll-like receptors (TLRs) plays crucial roles in the polarization of adaptive immune responses. A synthetic Toll-like receptor 2 (TLR2) ligand, Pam3CSK4, has been reported to m...It has been proposed that activation of Toll-like receptors (TLRs) plays crucial roles in the polarization of adaptive immune responses. A synthetic Toll-like receptor 2 (TLR2) ligand, Pam3CSK4, has been reported to modulate the balance of Th1/Th2 responses. We evaluated the modulation effect of Pam3CSK4 on allergic immune response in a mouse rhinitis model sensitized to house dust mite allergen (HDM). Mice were sensitized and challenged with Dermatophagoides farinae allergen (Der f), and then the allergic mice were treated by Pam3CSK4. Nasal allergic symptoms and eosinophils were scored. Der f-specific cytokine responses were examined in the splenocytes and bronchoalveolar lavage fluid (BALF). Serum level of total IgE was also detected. After establishing a mouse allergic rhinitis model with HDM, we have showed that Pam3CSK4 treatment not only ameliorated the nasal allergic symptoms remarkably but also decreased the eosinophils and total inflammation cells in BALF significantly. Analysis of cytokine profile found that IFN-γ released from either BALF or stimulated splenocytes increased markedly in Pam3CSK4-treated mice, while IL-13 decreased significantly. Moreover, serum level of total IgE was significantly lower in Pam3CSK4-treated mice than in the untreated. Thus, in an allergic rhinitis mouse model developed with HDM, Pam3CSK4 was shown to exhibit an antiallergic effect, indicating its potential application in allergic diseases.展开更多
Toll样受体(Toll like receptors,TLRs)是近年发现并倍受关注的一种识别受体。人们发现其在先天性和获得性免疫应答过程中起到链接点的作用,因此,TLRs在免疫学领域内具有重要地位。目前对TLRs的研究涉及到其结构、配体、信号通路以及临...Toll样受体(Toll like receptors,TLRs)是近年发现并倍受关注的一种识别受体。人们发现其在先天性和获得性免疫应答过程中起到链接点的作用,因此,TLRs在免疫学领域内具有重要地位。目前对TLRs的研究涉及到其结构、配体、信号通路以及临床应用等。现就TLRs目前的研究进展作一综述。展开更多
Background Toll-like receptors play an important role in the human immune system. This study was conducted to investigate the expression profiles and function of Toll-like receptor （TLR）1-9 in human corneal epitheli...Background Toll-like receptors play an important role in the human immune system. This study was conducted to investigate the expression profiles and function of Toll-like receptor （TLR）1-9 in human corneal epithelium. Methods The expression of TLR1-9 mRNA in 20 human donor corneal epithelia samples abraded during photorefractive keratotomy （PRK） and cultivated telomerase-immortalized human corneal epithelial cells （THCEs） was examined by semi-quantitative reverse-transcriptase polymerase chain reaction （RT-PCR） analysis. Human peripheral blood mononuclear cells （PBMCs） were used as positive controls. The expression of the TLR2 and TLR4 proteins was detected by Western analysis. ELISA was used to detect IL-8 secretion from THCEs challenged with ligands for TLR3 and TLR4 with and without antibody blockade. Results The expression of TLR1-9 at the mRNA level was detected in the epithelia of 20 patients and in THCE. Significant differences among individuals were observed. One patient was found to lack of the expression of TLR3, 4, 6 and 8, whereas another did not express TLRS. The expression of TLR2 and TLR4 protein was detected in human corneal epithelial cells. As THCE cells express TLR1-9, cells were challenged with lipopolysaccharides （LPS） and poly I：C to determine whether TLR4 and TLR3 were functional. The results showed that secretion of IL-8 by cells stimulated with LPS and Poly I：C was 7 to 10 fold greater than secretion by unchallenged cells. Blocking TLR4 with an anti-TLR4 antibody significantly inhibited the LPS-induced IL-8 production by THCE （P〈0.05）. Conclusion Human corneal epithelial cells express multiple TLRs and are able to recognize LPS and poly I：C. Different expression profiles among individuals suggest that differences in the susceptibilities and sensitivities to bacterial and viral infection in human populations relate to different patterns of TLR expression.展开更多
OBJECTIVE: To investigate the mechanism underlying anti-inflammatory and immunoregulatory effect of total glucosides of paeony(TGP) based on toll-like receptor 2(TLR2) mediated tumor necrosis factor(TNF) receptor-asso...OBJECTIVE: To investigate the mechanism underlying anti-inflammatory and immunoregulatory effect of total glucosides of paeony(TGP) based on toll-like receptor 2(TLR2) mediated tumor necrosis factor(TNF) receptor-associated factor 6(TRAF6)/nuclear factor-kappa B(NF-κB) pathway activation in rats with rheumatoid arthritis.METHODS: Adjuvant arthritis(AA) model was developed by complete freund’s adjuvant(CFA) immunization. TGP(100, 50, 25 mg/kg) and celecoxib(2.8 mg/kg) were administered by intragastric administration for 21 d. Right hind paw swelling was assessed every 2 d. After 21 d, synovial changes of the ankle were detected by histopathology. CD4+and CD8+ T cell amounts in peripheral blood were measured by flow-cytometrically. Gene and protein levels of toll-like receptor(TLR)2, TRAF6, tumor necrosis factor ligand superfamily member 6(FASLG)in the spleen were assessed by RT-qPCR and Western Bolt, respectively. Nuclear expression of NF-κB p65 was detected by NF-κB p65 Assay Kit.RESULTS: Paw swelling and synovium lesions were obviously aggravated in AA rats. These symptoms were significantly relieved by TGP.The ratio of CD4+/CD8+ T cell was increased in AA rats, while TGP reduced this increased ratio.Gene and protein levels of splenic TLR2, TFAR6 and FASLG, and nuclear NF-κB p65 in AA rats were significantly increased, but overtly inhibited by TGP.CONCLUSION: These findings suggest that TGP’s anti-inflammatory effect onRA in rats with CFA may be related to the downregulation of TLR2/TRAF6/NF-κB pathway and the regulation of T cell subsets.展开更多
基金Project (No. 39800135) supported by the National Natural ScienceFoundation of China
文摘It has been proposed that activation of Toll-like receptors (TLRs) plays crucial roles in the polarization of adaptive immune responses. A synthetic Toll-like receptor 2 (TLR2) ligand, Pam3CSK4, has been reported to modulate the balance of Th1/Th2 responses. We evaluated the modulation effect of Pam3CSK4 on allergic immune response in a mouse rhinitis model sensitized to house dust mite allergen (HDM). Mice were sensitized and challenged with Dermatophagoides farinae allergen (Der f), and then the allergic mice were treated by Pam3CSK4. Nasal allergic symptoms and eosinophils were scored. Der f-specific cytokine responses were examined in the splenocytes and bronchoalveolar lavage fluid (BALF). Serum level of total IgE was also detected. After establishing a mouse allergic rhinitis model with HDM, we have showed that Pam3CSK4 treatment not only ameliorated the nasal allergic symptoms remarkably but also decreased the eosinophils and total inflammation cells in BALF significantly. Analysis of cytokine profile found that IFN-γ released from either BALF or stimulated splenocytes increased markedly in Pam3CSK4-treated mice, while IL-13 decreased significantly. Moreover, serum level of total IgE was significantly lower in Pam3CSK4-treated mice than in the untreated. Thus, in an allergic rhinitis mouse model developed with HDM, Pam3CSK4 was shown to exhibit an antiallergic effect, indicating its potential application in allergic diseases.
文摘Toll样受体(Toll like receptors,TLRs)是近年发现并倍受关注的一种识别受体。人们发现其在先天性和获得性免疫应答过程中起到链接点的作用,因此,TLRs在免疫学领域内具有重要地位。目前对TLRs的研究涉及到其结构、配体、信号通路以及临床应用等。现就TLRs目前的研究进展作一综述。
基金This work was supported by grants from the National Natural Science Foundation of China(No.30328026 and No.30571997).
文摘Background Toll-like receptors play an important role in the human immune system. This study was conducted to investigate the expression profiles and function of Toll-like receptor （TLR）1-9 in human corneal epithelium. Methods The expression of TLR1-9 mRNA in 20 human donor corneal epithelia samples abraded during photorefractive keratotomy （PRK） and cultivated telomerase-immortalized human corneal epithelial cells （THCEs） was examined by semi-quantitative reverse-transcriptase polymerase chain reaction （RT-PCR） analysis. Human peripheral blood mononuclear cells （PBMCs） were used as positive controls. The expression of the TLR2 and TLR4 proteins was detected by Western analysis. ELISA was used to detect IL-8 secretion from THCEs challenged with ligands for TLR3 and TLR4 with and without antibody blockade. Results The expression of TLR1-9 at the mRNA level was detected in the epithelia of 20 patients and in THCE. Significant differences among individuals were observed. One patient was found to lack of the expression of TLR3, 4, 6 and 8, whereas another did not express TLRS. The expression of TLR2 and TLR4 protein was detected in human corneal epithelial cells. As THCE cells express TLR1-9, cells were challenged with lipopolysaccharides （LPS） and poly I：C to determine whether TLR4 and TLR3 were functional. The results showed that secretion of IL-8 by cells stimulated with LPS and Poly I：C was 7 to 10 fold greater than secretion by unchallenged cells. Blocking TLR4 with an anti-TLR4 antibody significantly inhibited the LPS-induced IL-8 production by THCE （P〈0.05）. Conclusion Human corneal epithelial cells express multiple TLRs and are able to recognize LPS and poly I：C. Different expression profiles among individuals suggest that differences in the susceptibilities and sensitivities to bacterial and viral infection in human populations relate to different patterns of TLR expression.
基金Supported by Natural Science Foundation of China(No.81273900):Studies on Epigenetic Mechanisms Associated with the Classical Decoction of HanBi(Wutou Decoction)and ReBi(Baihu Plus Guizhi Decoction)Natural Science Foundation of China(No.81773972):Based on succinate/GPR91 Pathway Connected Abnormal Glucose Metabolism Exacerbates Inflammation to Investigate the"Dispelling Pyretic Arthralgia"Mechanism of Baihu Guizhi Decoction
文摘OBJECTIVE: To investigate the mechanism underlying anti-inflammatory and immunoregulatory effect of total glucosides of paeony(TGP) based on toll-like receptor 2(TLR2) mediated tumor necrosis factor(TNF) receptor-associated factor 6(TRAF6)/nuclear factor-kappa B(NF-κB) pathway activation in rats with rheumatoid arthritis.METHODS: Adjuvant arthritis(AA) model was developed by complete freund’s adjuvant(CFA) immunization. TGP(100, 50, 25 mg/kg) and celecoxib(2.8 mg/kg) were administered by intragastric administration for 21 d. Right hind paw swelling was assessed every 2 d. After 21 d, synovial changes of the ankle were detected by histopathology. CD4+and CD8+ T cell amounts in peripheral blood were measured by flow-cytometrically. Gene and protein levels of toll-like receptor(TLR)2, TRAF6, tumor necrosis factor ligand superfamily member 6(FASLG)in the spleen were assessed by RT-qPCR and Western Bolt, respectively. Nuclear expression of NF-κB p65 was detected by NF-κB p65 Assay Kit.RESULTS: Paw swelling and synovium lesions were obviously aggravated in AA rats. These symptoms were significantly relieved by TGP.The ratio of CD4+/CD8+ T cell was increased in AA rats, while TGP reduced this increased ratio.Gene and protein levels of splenic TLR2, TFAR6 and FASLG, and nuclear NF-κB p65 in AA rats were significantly increased, but overtly inhibited by TGP.CONCLUSION: These findings suggest that TGP’s anti-inflammatory effect onRA in rats with CFA may be related to the downregulation of TLR2/TRAF6/NF-κB pathway and the regulation of T cell subsets.
